The specific aim of this proposal is to probe the biosynthesis of novel prenylated alkaloids containing a [2.2.2] bridged diketopiperazine ring system. Of particular interest to this program are avrainvillamide, a cytotoxic marine alkaloid, and stephacidin B, a potent inhibitor of testosterone-dependent prostate LNCaP cells. During the proposal period, an effort will be made to develop a complete biosynthetic picture of each natural product. Considering that stephacidin B appears to be a dimer of avrainvillamide, a special emphasis will be placed upon exploring the nature of the dimedzation and its role during the biosynthesis of stephacidin B. In order to provide validity to our biosynthetic claims, several synthetic and radiolabelled experiments that will be conducted are described. In addition to the biosynthetic investigation, a biomimetically patterned total synthesis of stephacidin B will be carried out in order to further explore the medicinal properties of this complex natural product.